ALLG Wrap-up @ ASH2019

 In News, Scientific Meeting

The ALLG had a strong presence at the ASH annual meeting in Orlando this week (Dec 5-10, 2019). ASH is the world’s largest haematology conference is the key meeting place for the ALLG to not only keep up-to-date with the latest developments, but also meet with international collaborative research groups such as American and Canadian cooperative research groups and many international haematology experts. Raising the ALLG profile by promoting our research and bringing international clinical trials to Australia are key objectives for ALLG Members.

ash-2019

Prof Andrew Roberts named Deputy Editor of Blood journal

Congratulations to ALLG director, Prof Andrew Roberts, for being named Deputy Editor of the prestigious Blood journal. The American Society of Hematology (ASH) made the announcement about its flagship journal during its annual conference in Orlando this week. Prof Roberts will assume the editorial position in 2020, replacing the current Deputy Editor Dr Nancy Berliner (Brigham and Women’s Hospital, Boston, MA), who will move to Editor-in-Chief upon the retirement of Prof Bob Löwenberg.

In May 2019, the ALLG and Prof Roberts hosted Prof Löwenberg for the ALLG’s “AML in 2019 and Beyond” event in Melbourne. See highlights from “AML in 2019 and Beyond“.

Prof Andrew Roberts

ALLG director and 20-year member, Prof Andrew Roberts, has been named the new Deputy Editor of Blood.

Posters & Presentations in Orlando

Congratulations to the following ALLG Members and their teams who presented ALLG-related research at ASH this year.

ALL08

Preliminary Minimal Residual Disease Analysis of the Australasian Leukaemia & Lymphoma Group (ALLG) ALL8 Study of Front-Line Blinatumomab with Chemotherapy in Adults with Ph Negative B-Cell Acute Lymphoblastic Leukaemia.

Authors: Shaun Fleming, Nicola Venn, John Reynolds, Uyen Nguyen, John Kwan, John Moore, David T Yeung, Michael F. Leahy, Matthew Greenwood, Emma Verner, Ashish Bajel, Leanne Berkahn, Andrew H. Wei, and Rosemary Sutton.

Summary: Front-line therapy with blinatumomab in combination with chemotherapy is feasible in adults and results in high levels of MRD response by the end of the first consolidation block with the majority of MRD negative responses attained after the first treatment block. Despite early incorporation of blinatumomab into this treatment protocol, MRD progression was seen in one patient with high-risk cytogenetic abnormalities.

ALLG ALL08 Schema

ALLG ALL08 Treatment Schema as presented at ASH2019.

MM14

Identification of Novel Immune Cell Populations in Lenalidomide Refractory Relapsed Multiple Myeloma Patients Treated with Pomalidomide and Low Dose Dexamethasone.

Authors: Anna Kalff, Tiffany Khong, Malarmathy Ramachandran, Sam Norton, Andrew Mitchell, John Reynolds, Hang Quach, P Joy Ho, Noemi Horvath, Peter Mollee, Nola Kennedy, Roslyn Kemp and Andrew Spencer.

Summary: The ALLG MM14 trial evaluated the impact of low dose dexamethasone (LoDEX) withdrawal in lenalidomide (LEN) refractory and relapsed (RR) multiple myeloma (MM) patients achieving initial disease control with pomalidomide (POM) and LoDEX re-induction. As previously reported, patients continuing with POM LoDEX had superior progression free survival (PFS) compared to maintenance with POM alone, however, this early PFS benefit was lost and by 18m was reversed to favour POM only. In patients who received post-progression therapy, more durable responses (second PFS: 12.7m vs 4.6m, p=0.034) and superior survival (OS: 19.4m vs 12.5m, p=0.092) were seen in those previously treated with POM alone. Here we present findings from the preliminary correlative immune studies of this trial.

Utilising CyToF, we have identified a novel “NK B cell” population in RRMM patients, with a higher baseline frequency of these cells being associated with a greater likelihood of response to POM LoDEX. Importantly, we have also confirmed the presence of these cells in an independent MM cohort. Moreover, subsequent to POM LoDEX exposure we have demonstrated the enrichment of heterogeneous neutrophil populations as well as an increase in activated NK cells and commensurate decrease in inhibited NK cells. These novel observations may provide new insights into the mechanisms of action of pomalidomide in MM.

NHL21

Interim Circulating Tumor DNA As a Prognostic Biomarker in the Setting of Interim PET-Based Adaptive Therapy for DLBCL.

Stephen Opat and Charles Macaulay pose in front of their NHL21-related poster at ASH2019.

Authors: Charles Macaulay, Stefan Alig, David M. Kurtz, Michael C. Jin, Stephen Opat, Joanne Soo, Brian Sworder, Mark S. Hertzberg, Maher K. Gandhi, Maximilian Diehn, and Ash A Alizadeh.

Summary: Charles Macaulay and Stephen Opat presented work relating to samples from the ALLG NHL21 trial, for which Prof Mark Hertzberg is the CI.

Late in the course of DLBCL therapy, ctDNA carries promising value as a biomarker for stratifying predicted patient response to therapy as evidenced by additional detection of additional 50% detection of relapsing cases not categorized as iPET-positive. Data from additional patients and relationships between ctDNA response as measured by EMR (C2D1), MMR (C3D1), and C4D1 will be presented at the meeting.

MM17

Andrew Spencer and Delaine Smith smile for the camera at the MM17 poster at ASH2019.

A Longitudinal Evaluation of Euroflow and Combined Quantitative Immunoprecipitation (QIP) and Free Light Chain (FLC) Mass Spectometry (MS) in Functional High Risk Multiple Myeloma.

Authors: Andrew Spencer, Tiffany Khong, Flora Yuen, Hannah Victoria Giles, Malgorzata Gorniak, Hang Quach, Noemi Horvath, Ian H. Kerridge, Edwin Sze-Hung Lee, Krystal Bergin, Shreerang Sridesai, Anna Kalff, and John Reynolds.

Summary: These preliminary data confirm the utility of QIP MS and FLC MS for the sequential monitoring of tumour burden in HR MM. Concordance with standard monitoring was good with MS detectable disease in some patients with serological sCR/CR consistent with the higher sensitivity of MS. Concordance with NGF was only fair to moderate mandating the future comparison of larger sample sets to better understand the relationship between the 2 methodologies.

MM18

Higher Intensity of Cell Surface Glucose-Regulated Protein 78 (csGRP78) Expression Is Seen in Patients with Early Progressive Disease/Mortality in a Cohort of Relapsed, Refractory Multiple Myeloma Patients Treated with Carfilzomib, Thalidomide and Dexamethasone.

Authors: Slavisa Ninkovic, Simon Harrison, Lenny Straszkowski, Giulia Quattrocchi, Wee-Joo Chng, Louise E. Purton, and Hang Quach.

Summary: Here we demonstrate that cell surface expression of GRP78 is prominent in both the plasma cells and cells of the tumour microenvironment in patients with RRMM and persists in the TME cells in patients on treatment. Early (<6mo) disease progression or mortality is associated with higher baseline intensity of global cell surface GRP78 expression. Additional studies are being performed to evaluate the promise of cell surface GRP78 expression on plasma cells as a potential biomarker of response to therapy.

NHL29

Response Rates and Quality of Life Outcomes in Australasian Leukaemia & Lymphoma Group NHL29: A Phase II Study of Ibrutinib, Rituximab and Mini-CHOP in Very Elderly Patients with Newly Diagnosed Diffuse Large B Cell Lymphoma.

Authors: Emma Verner, Amanda Johnston, Nalini Pati, Eliza A Hawkes, Hui-Peng Lee, Tara Cochrane, Chan Y. Cheah, Duncan Purtill, Anoop K Enjeti, Christina Brown, Nicholas E. Murphy, Jennifer Curnow, Julia Carlson, Belinda Butcher, and Judith Trotman.

Summary: Albeit with considerable toxicity and early mortality, Ibrutinib-R mini-CHOP is a deliverable and effective treatment for most pts ≥75yrs with DLBCL. While longer follow-up is required to assess our primary efficacy endpoint of 2yr overall survival, this promising response and reassuring QoL data highlights the merits of ongoing study to identify deliverable and effective treatments for DLBCL in the very elderly.

CML11

Combination of Nilotinib and Pegylated Interferon Alfa-2B Results in High Rates of MR4.5 at 24 Months – Primary Analysis of the ALLG CML11 Pinnacle Study.

From left: Naranie Shanmuganathan, Tim Hughes, Agnes Yong and Sue Branford show off their CML11 poster session at ASH2019.

Authors: David T Yeung, Naranie Shanmuganathan, Andrew Grigg, Ilona Cunningham, Jake Shortt, Philip Rowling, John Reynolds, Rosemary Anne Harrup, David M Ross, David Kipp, Anthony K Mills, Christopher K Arthur, Anthony P Schwarer, Kathryn Jackson, Nicholas Viiala, Robert Weinkove, Agnes S. M. Yong, Deborah L. White, Susan Branford, Timothy P. Hughes, and On Behalf of the ALLG.

Summary: Combination therapy with NIL and Peg-IFN leads to favourable rates of molecular responses that may be superior to NIL monotherapy. While the majority of patients did not durably tolerate full dose Pegintron, there was minimal interference with TKI dose intensity. Such strategies may maximise achievement of deep molecular response, allowing a trial of TKI cessation and the benefit of treatment free remission to an increased number of patients.

CML12

Prof Tim Hughes presented the CML12 poster at ASH2019.

Pro-Active Dasatinib Dose Reduction Based on Trough Levels May Minimise Toxicity and Preserve Efficacy – Interim Analysis of the ALLG CML12 Direct Study.

Authors: David T Yeung, Andrew Grigg, Naranie Shanmuganathan, Ann Christine Solterbeck, Deborah L. White, Susan Branford, Nicholas Viiala, Philip Arthur Rowlings, Anthony K Mills, Jake Shortt, Campbell Tiley, David M Ross, David Kipp, Rosemary Anne Harrup, Ilona Cunningham, John Kwan, Richard Eek, Howard Mutsando, Ken-Soon Tan, Kate Burbury, Matthew P.F. Wright, Timothy P. Hughes, and On Behalf of the ALLG.

Summary: The DIRECT study demonstrated the feasibility of using dasatinib Cmin levels to optimise dosing. Early molecular response rates are encouraging and predict for excellent achievement of long-term molecular response. Long term efficacy and safety data are awaited.

Late-breaking Presentations

A/Prof Andrew Wei, Chair of the ALLG’s Acute Leukaemia Working Party and Ambassador for the National Blood Cancer Registry (NBCR), spoke at the Friday Satellite Symposia about “Data + Perspectives: Exploring the Role of Novel Agents and Emerging Strategies in the Management of Acute Myeloid Leukemia” and delivered a late-breaking abstract presentation at ASH in Orlando on the CC-486 (azacitine oral formulation) for acute myeloid leukaemia in first remission.

View Andrew’s Abstract Presentation.

A/Prof Andrew Wei

A/Prof Andrew Wei presenting to the ASH audience in Orlando.